Download Evaluation of Creatine Kinase as A diagnostic Tool

DOI: 10.21276/sjams.2016.4.8.67
Scholars Journal of Applied Medical Sciences (SJAMS)
Sch. J. App. Med. Sci., 2016; 4(8E):3079-3082
ISSN 2320-6691 (Online)
ISSN 2347-954X (Print)
©Scholars Academic and Scientific Publisher
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Original Research Article
Evaluation of Creatine Kinase as A diagnostic Tool for Thyroid Disorders
Mohammed A.F Alriyah1, Nasser Eldin M.A. Shrif2
Department of clinical chemistry, Faculty of medical laboratory science, Alneelain University, Khartoum, Sudan
2
Department of clinical chemistry, Faculty of medical laboratory science, Alzaeem Alazhary University, Khartoum,
Sudan
1
*Corresponding author
Mohammed A.F Alriyah
Email: [email protected]
Abstract: There is evidence of opposite relationship between creatine kinase and thyroid dysfunction disorders. This
study aimed to evaluate serum CK level in hypothyroidism and hyperthyroidism patients and find its correlations with
thyroid function tests. In this cross-sectional study 200 hundred subjects diagnosed with thyroid dysfunctions referred to
advanced diagnostic center-Khartoum- Sudan were involved. A 100 had hypothyroidism aged 35±10) years while other
100 ones had hyperthyroidism aged (42+11) years. Laboratory analysis of thyroid function tests (TFT) via i-chroma,
device, an immuno chromo genic process, and serum CK enzyme activity measurement via spectrophotometer, Bio
system device were performed for all participants. Statistical analysis for the data obtained was conducted via spss
program version 16. The CK activity level was significantly increased in hypothyroid patients compared to
hyperthyroidism patients (183.2±34.2vs 47.2±12.6, p.value 0.001). In hypothyroidism patients, the serum activity level
positively correlated with TSH level. In hyperthyroidism patients there was negative correlation between CK activity and
duration of the disease. CK is considered a marker for variety of systems abnormalities as muscular damage and others,
it could be used as monitor for thyroid dysfunction treatment state.
Keywords: thyroid dysfunction, CK activity.
INTRODUCTION:
The multiple hormones regulates almost all
body functions, including metabolism, growth and
development [1].The thyroid secretes two major
hormones, thyroxine and triiodothyronine, commonly
called T4 and T3, respectively. Both of these hormones
profoundly increase the metabolic rate of the body.
Complete lack of thyroid secretion usually causes the
basal metabolic rate to fall 40-50% below normal, and
extreme excesses of thyroid secretion can increase the
basal metabolic rate to 60-100% above normal. Thyroid
secretion is controlled primarily by thyroid-stimulating
hormone (TSH) secreted by the anterior pituitary gland.
The thyroid gland is unusual among the endocrine
glands in its ability to store large amounts of hormone.
After synthesis of the thyroid hormones has run its
course, each thyroglobulin molecule contains up to 30
T3 molecules and a few T4 molecules. In this form, the
thyroid hormones are stored in the follicles in an
amount sufficient to supply the body with its normal
requirements of thyroid hormones for 2 to 3 months.
Therefore, when synthesis of thyroid hormone ceases,
the physiologic effects of deficiency are not observed
for several months [1].
Thyroid disorders can range from a slightly
enlarged thyroid gland that needs no treatment to lifethreatening thyroid cancer. The most common thyroid
problems involve the abnormal production of thyroid
hormones. Thyroid function disorders can generally be
grouped into two classes [2]: Hypothyroidism is defined
as failure of the thyroid gland to produce sufficient
thyroid hormone to meet the metabolic demands of the
body [3]. The prevalence increases with age, and is
higher in females than in males [4] while
Hyperthyroidism: Over activity of the thyroid gland
leads to high levels of thyroid hormones and the
speeding up of the metabolism. The heart rate and blood
pressure may increase, heart rhythms may be abnormal,
and patients may sweat excessively, feel nervous and
anxious, have difficulty sleeping, and loss of weight
without dieting. Graves’ disease (toxic diffuse goitre) is
the most common cause of hyperthyroidism [5], it is
affecting approximately 2 percent of women and 0.2
percent of men [6]; the patient may have
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Mohammed AFA et al., Sch. J. App. Med. Sci., Aug 2016; 4(8E):3079-3082
triiodothyronine toxicosis [7]. Patients with subclinical
thyroid disease have few or no symptoms or signs of
thyroid dysfunction and thus by its very nature
subclinical thyroid disease is a laboratory diagnosis.
Subclinical hypothyroidism is defined as a serum
thyroid stimulating hormone (TSH) above the defined
upper limit of the reference range, with a serum free
thyroxine within the reference range. Other causes of a
raised TSH, a past history of thyroid disease and
patients on T4 hormone treatment need to be excluded.
It is therefore critically important that the reference
limits for TSH be standardised. The TSH method used
should have a high functional sensitivity (at least 0.02
mU/L), although this is of most importance for the
diagnosis of subclinical hyperthyroidism [8]. To
diagnose thyroid dysfunction, TSH should be used to
diagnose primary hypothyroidism [9]. While diagnosis
of hyperthyroidism is based on clinical examination and
TFT. Physical examination may reveal thyroid
enlargement, tremor, hyperactive reflexes or an
increased heart rate. The systolic blood pressure may be
elevated. Subclinical hyperthyroidism is defined as a
mild form of hyperthyroidism that is diagnosed by
abnormal blood levels of thyroid hormones; often in the
absence of any symptoms typically there are low TSH
and elevated T3 and T4 [10].
Creatine kinase (CK) is a compact enzyme and
it is found in both the cytosol and mitochondria of
tissues where energy demands are high. In the cytosol,
CK is composed of two polypeptide subunits and two
types of subunit are found, M (muscle type) and B
(brain type). These subunits allow the formation of
three tissue-specific isoenzymes: CK-MB (cardiac
muscle), CK-MM (skeletal muscle), and CK-BB (brain)
[11]. (CK) is a central controller of cellular energy
homeostasis. By reversible interconversion of creatine
into phosphocreatine, CK builds up a large pool of
rapidly diffusing phosphocreatine for temporal and
spatial buffering of ATP levels. Thus, CK plays a
particularly important role in tissues with large and
fluctuating energy demands like muscle and brain [12].
Further functions of CK are based on the concepts of
subcellular compartmentation of CK isoenzymes and
limitations of free diffusion even of smaller molecules
within the cell as, adenine nucleotides [13]. Raised
levels of serum CK are still closely associated with cell
damage, muscle cell disruption, or disease [14], and that
has been found in thyroid dysfunction states by many
studies conducted in order to assess parameters beside
monitoring TFT in those patients, typically in
hypothyroidism CK activity increased, while in
hyperthyroidism decreased [15, 16].
MATERIAL AND METHOD
In this cross-sectional study, 200 hundred
subjects diagnosed with thyroid dysfunctions referred to
advanced diagnostic center-Khartoum- Sudan were
involved. From them , 100 subjects
had
hypothyroidism were 75% males and 25% female, the
(mean+SD) of age as (35+10) years while other 100
ones had hyperthyroidism, were 68% males and 32%
female and the (mean+SD) of age as (42+11) years . A
formal consent obtained from the patients and ethical
clearance from local authorities was obtained. 5 ml of
blood was withdrawal from each subject under hygienic
environment, allowed for auto-serum formation,
separation and preserved at -20Co for subsequent
analysis of thyroid function tests (TFT) via i-chroma,
device, an immunochromogenic process and
measurement of CK enzyme via spectrophotometer,
Biosystem device and reagent. Analytical process
conducted in faculty of medical laboratory scienceAlneelain University, department of clinical chemistry.
Statistical analysis of data conducted via SPSS program
version 16
RESULT
This study involved a 200 thyroid dysfunction
subjects attended to advanced diagnostic center,
involved in this study, 100 patients were diagnosed with
hypothyroidism, their Mean ±SD disease duration was
(2.3±1.4) years and the other 100 subjects were
diagnosed with hyperthyroidism and their Mean±SD of
disease duration was (2.7±1.8 years). The comparison
of T3, T4, TSH and CK enzyme activity measurements
between two groups are shown in table1. CK showed
positive Correlation with TSH in hypothyroidism
patients and negative correlation with duration of the
disease in hyperthyroidism patients (Table 2)
Table-1: Comparison of study parameters between hypo- and hyperthyroidism patients.
Parameters
Hypothyroid
Hyperthyroid
P value
Mean+SD
Mean+SD
T3
0.194+0.28
4.5+1.6
.000
T4
2.94+1.96
17.9+3.8
.000
TSH
17.8+10.5
0.14+0.01
.000
CK
182.3+34.2
47.2+12.6
.001
Student T. test was used to calculate P. value, P. value less than 0.05 was considered Significant
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Mohammed AFA et al., Sch. J. App. Med. Sci., Aug 2016; 4(8E):3079-3082
Table 2: Correlation of CK with age, duration, T3, T4, TSH in hypo and hyperthyroid patients
CK
Age
duration
T3
T4
TSH
Hyperthyroid
-.116
-.243*
.000
-.032
.062
Hypothyroid
.197
.006
-.027
-.104
.478**
**Correlation is significant at the 0.01 level (2-tailed), *Correlation is significant at the 0.05 level (2-tailed)
.
DISCUSSION
REFERENCE
This study was conducted to evaluate the
1. Hall J.E; Guyton and Hall, text book of medical
creatine kinase enzyme level among patients with
physiology, Elsevier Health Sciences. Chapter
thyroid dysfunction whether hyperthyroidism or
74&76; 2015; 906&931-936.
hypothyroidism, included hundred (100) subjects for
2. Beers MH, Porter RS, Jones TV, et al.; editors. The
each group. Both genders were participants. In this
Merck Manual. 18th ed. Whitehouse Station:
study, thyroid dysfunction distributed among males
Merck Research Laboratories; 2006.
more than females, this disagrees with a study
3. Hollowell JG, Staehling NW, Flanders WD,
conducted on hypothyroidism subjects, female were
Hannon W.H, Gunter E.W, Spencer C.A et al.;
more than males [17]. The outcome of this study
Serum TSH, T(4), and thyroid antibodies in the
showed the state of CK enzyme among each thyroid
United States population (1988 to 1994): National
dysfunction group besides monitoring TFT. In primary
Health and Nutrition Examination Survey
hypothyroidism patients as decreased levels of both T3
(NHANES III). J ClinEndocrinolMetab. 2002;
and T4 and increased TSH, CK level was elevated. The
87(2):489–499.
activity of CK is correlated with TSH level. However,
4. Boucai L, Hollowell JG, Surks MI; An approach
in hyperthyroidism the activity was not affected and
for development of age-, gender-, and ethnicitywas negatively correlated with durations of the study.
specific thyrotropin reference limits. Thyroid.
These findings agree with previous studies [18], many
2011; 21(1):5–11.
mechanisms can causing
increase of ck among
5. Muller AF, Berghout A, Wiersinga WM, Kooy A,
hypothyroid patients, one of this mechanism, skeletal
Smits J.W, Hermus A.R.M.M; Thyroid function
muscle is effected by hypothyroidism because T3and
disorders – guidelines of the Netherlands
T4 regulate and control the metabolic activity of
Association of Internal Medicine. Neth J Med.
creatine kinase, therefore decrease level of thyroid
2008; 66(3):134- 142.
hormone lead to uncontrollable creatine kinase and it
6. Tunbridge WMG, Evered DC, Hall R, Appleton D,
increase
in
circulation
[19]
patients
with
Brewis M, Clark F et al.; The spectrum of thyroid
hypothyroidism are suffer from myopathy due to
disease in a community: the Whickham survey.
hypometabolic state , that lead to reduction in oxidative
Clin Endocrinol (Oxf) 1977; 7(6):481-493.
phosphorylation and glycolysis and reduction of ( ATP)
7. Ruiz M, Rajatanavin R, Young RA, Taylor C,
below the normal limit that lead to increase cell
Brown R, Braverman L.E et al.; Familial
permeability and leakage creatine kinase from cell to
dysalbuminemic hyper thyroxinemia: a syndrome
circulation due to alteration of sarcolemmal
that can be confused with thyrotoxicosis. NEngl J
membranes, CK-MM isoenzyme increased in
Med 1982; 306:635-639.
hypothyroid that lead to increase of C.K activity which
8. Hollowell JG, Staehling NW, Flanders WD,
marker of skeletal muscle abnormality, and it major
Hannon WH, Gunter EW, Spencer CA, et al.;
source of elevation serum creatine kinase [20-22]
Serum TSH, T(4), and thyroid antibodies in the
concentration with other studies conducted in
United States population (1988 to 1994): National
monitoring drug administration in hyperthyroid state
Health and Nutrition Examination Survey
which it revealed that the CK level increased was while
(NHANES III).J ClinEndocrinolMetab. 2002 Feb;
thyroid hormones targeted to be low, suggesting that
87(2):489-99.
increased CK level parallel with decreased thyroid
9. Spencer CA; Clinical utility and cost-effectiveness
hormones levels [16, 23] While disagreement with
of sensitive thyrotropin assays in ambulatory and
study involved both thyroid dysfunctions in order to
hospitalized patients. Mayo Clin Proc. 1988;
monitor serum hormones levels, one of them was CK,
63(12):1214-1222.
which found significant elevated in both hypo and
10. Reid JR, Wheeler SF; Hyperthyroidism: diagnosis
hyperthyroidism [24].
and treatment. Am FAM Phys. 2005; 72(4):623630.
11. Schlattner U, Tokarska-Schlattner M, Wallimann
CONCLUSION
As CK is considered a marker for variety of
T; Mitochondrial creatine kinase in human health
systems abnormalities as muscular damage and others,
and disease,” Biochemica ET Biophysica Acta—
it could be used as supportive parameter to diagnosing
Molecular Basis of Disease, 2006; 1762(2): 164–
thyroid dysfunction ,hypothyroidism screening and in
180.
thyroid treatment states.
3081
Mohammed AFA et al., Sch. J. App. Med. Sci., Aug 2016; 4(8E):3079-3082
12. Ellington W; Evolution and physiological roles of
phosphagen systems Annu. Rev. Physiol., 2001;
63: 289–325.
13. Wallimann T, Wyss M, Brdiczka D, Nicolay K,
Eppenberger H.M; Eppenberger Intracellular
Compartmentation, structure and function of
creatine kinase isoenzymes in tissues with high and
fluctuating energy demands: the ‘phosphocreatine
circuit’ for cellular energy homeostasis Biochem J,
1992; 281: 21–40.
14. Totsuka M, Nakaji S, Suzuki K, Sugawara K, Sato
K; Break point of serum creatine kinase release
after endurance exercise,” Journal of Applied
Physiology, 2002; 93(4): 1280–1286.
15. Mythili SV, Ravisekar P, Shanthi B, Kalaiselvi V,
Manjuladevi AJ; Serum Creatine Kinase Activity
in Thyroid Disorders. Research Journal of
Pharmaceutical, Biological and Chemical Sciences.
RJPBCS 2014; 5(5): 669.
16. Suzuki S, Ichikawa K, Nagai M, Mikoshiba M,
Mori J.I, Kaneko A et al.; Elevation of Serum
Creatine Kinase During Treatment With
Antithyroid
Drugs
in
Patients
With
Hyperthyroidism Due to Graves’ Disease A Novel
Side Effect of Antithyroid Drugs. Arch Intern Med.
1997; 157(6):693-696.
17. Imtiaz M.A, Reshma S, Gopal M, Monteiro F.N;
Renal and muscular dysfunction in subclinical
hypothyroidism. 2015; 48(2): 8384-8387.
18. Ranka R, Mathur R; Serum creatine phosphokinase
in thyroid disorders. Indian Journal of Clinical
Biochemistry, 2003; 18(1): 107-110.
19. Giampietro O, Clerico A, Buzzigoli G, Del Chicca
MG, Boni C, Carpi A; Detection of hypothyroid
myopathy by measurement of various serum
muscle markersmyoglobin, creatine kinase, lactate
dehydrogenase and their isoenzymes. Correlations
with thyroid hormone levels (free and total) and
clinical usefulness. Horm Res 1984; 19(4):232-42.
20. Soufir JC, Zbranca TE, Bernheim R, Perlemuter L,
Hazard J; Nouv Presse Med 1975;4:3055-9.
21. Hartl E, Finstere J, Grossegger C, Kroiss A,
Stöllberger C; Endocrinologist 2001;11:217-21.
22. Del Palacio A, Truea JL, Cabello A, Gutiérrez E,
Moya I, Fernández Miranda C, et al.; Ann Med
Intern (Madrid) 1990;7:115-9.
23. Uçan B, Yüksek C, Kizilgul M, Erten R, Konuk G,
Mercan Z, et al.; Creatine Kinase Elevation during
Antithyroid Treatment of a Patient with Graves’
Disease: A Case Report and Review of Literature.
Exp Clin Endocrinol Diabetes Rep 2015; 02(03):
e14-e16
24. Pandey R, Jaiswal S, Sah J.P, Bastola K, Dulal S;
Assessment of Serum Enzymes Level in Patients
with Thyroid Alteration Attending Manipal
Teaching Hospital, Pokhara. Thyroid, 2013; 10: 12.
3082